Unbounding the Future:
the Nanotechnology Revolution

Chapter 5

The Threshold of
Nanotechnology

In the last chapter, we looked at the state of
current research, but from there to the nanotechnology of even
the Pocket Library scenario is a leap. How will this gap be
crossed?

In this chapter, we outline how emerging
technologies can lead to nanotechnology. The actual path to
nanotechnologythe one that history books will
recordcould emerge from any one of the research directions
in physics, biochemistry, and chemistry recounted in the last
chapter, or (more likely) from a combination of them. The
availability of so many good options builds confidence that the
goal can be reached, even while it decreases confidence that some
particular path will be fastest. To see how advances might cross
the gap from present technology to early nanotechnology, let's
follow one path out of the many possible.

Bridging the Gap

One way to bridge the gap would through the
development of an AFM-based molecular
manipulator capable of doing primitive molecular
manufacturing. This device would combine a simple molecular
devicea molecular gripperwith an AFM positioning
mechanism. An AFM can move its tip with precision; a molecular
manipulator would add a gripper to the tip to hold a molecular
tool. A molecular manipulator of this kind would guide chemical
reactions by positioning molecules,
like a slow, simple, but enormous assembler. (In our standard
simulation view, where a molecular assembler arm fits in a room,
the AFM apparatus of a molecular manipulator would be the size of
a moon.) Despite its limits, an AFM molecular manipulator will be
a striking advance.

How might this advance occur? Since we're
choosing one path out of many possible, we may as well include
more details and tell a story. (A more technical description of a
device like the following can be found in Nature; see the technical bibliography).

Scenario: Developing a
Molecular Manipulator

Several years ago, researchers at the
University of Brobdingnag began work on developing a
molecular manipulator. To reach this goal, a team of a dozen
physicists, chemists, and protein researchers banded together
(some working full time, some part time) and began the
creative teamwork needed to solve the basic problems.

First they needed to attach a gripper to an
AFM tip. As grippers, they chose fragments of antibody
molecules, the selectively sticky proteins that the immune
system uses to bind and identify germs. If they could get the
"back" of the molecule stuck onto a tip, then the
"front" could bind and hold molecular tools. (The
advantage of antibody fragments was this: freedom of tool
choice. Since the late 1980s, researchers had been able to
generate antibodies able to bind almost any preselected
molecule-or molecular tool.) They tried half a dozen methods
before finding one that worked reliably, with results like
those shown in Figure 6. A graduate student got her Ph.D.,
and the AFM tip got its gripper.

FIGURE 6: MOLECULAR MANIPULATOR

A molecular manipulator (AFM tip and tool holder, above)
would bind and position reactive molecular tools to build
up a workpiece, molecule by molecule.

In parallel, the U. Brob AFM
researchers worked on placing tips in a precise location and
then holding them there with atomic accuracy for seconds at a
time. This proved straightforward. They used techniques
developed elsewhere during the early 1990s, adding only
modest refinements.

They now had their gripper and a way of
putting it where they wanted it, but they needed a set of
tools. The gripper was like the chuck of a drill, waiting to
have different bits fitted into its tool-holder slot. So as
the final step, the synthetic chemists on the team made a
dozen different molecular tools, all identical at one end but
different at the other. The similar parts all bound to the
same antibody tool-holder, slotting neatly into position. The
different parts were all chemically reactive in different
ways. Like the molecular tools in the hall of assembler arms
in Chapter 3, each of these tools
could use a chemical reaction to transfer some atoms to a molecular object
under construction.

Developing the molecular tool kit was the
toughest part of the project; it took about as much work as
had gone into duplicating the palytoxin molecule back in the
1980s. None of the tasks in the project demanded the solution
of a deep scientific puzzle, and none demanded the solution
of a notoriously difficult engineering problem. Each task had
many possible solutions, the problem was to find a compatible
set of solutions and apply them. After a few years, the
solutions came together and the U. Brob research team began
building new molecules by molecular manipulation. Now many
teams are doing likewise.

Building with Molecular
Grippers and Tools

To build something with the U. Brob team's
AFM-based molecular manipulator system, you use it as
follows: First, choose a surface to build on and place it
under the tip in a pool of liquid. Then dunk the AFM tip into
the liquid, bringing it down to the surface, and back it off
a little. Construction can now begin as soon as a tool is
loaded into the gripper.

Tubes and pumps can flow different liquids
over the surface and past the gripper, carrying different
tool molecules. If you want to do something with a tool of
Type A, you wash in the proper liquid, and a Type A molecule
promptly sticks the to the gripper as shown in Figure 6. Once
it is in the gripper, you can use the AFM mechanism to move
it around and put it where you want it. Move it up to the
surface at a convenient spot, wait a few seconds, and it
reacts, forming a bond and leaving a molecular fragment
attached to the spot you chose. To add a different fragment,
you can use a tool of Type B: you back up the tip, flow in a
fresh liquid carrying the new tools, and in a moment a tool
of the new type is bound in place and ready to apply, either
on or alongside the first spot. Step by step, you build up a
precise molecular structure.

Each step takes only seconds. Molecular tools
pop into the gripper in a fraction of a second, and used
tools pop off at the same rate. Once the tip has positioned a
molecule, it reacts quickly, about a million times faster
than unwanted reactions at other sites. In this way, the
molecular manipulator gives good control of where reactions
will occur (though it is not as reliable as an advanced
assembler would be). It is fairly fast by a chemist's
standardsper cyclebut still a million times
slower than an advanced assembler. It can perform a variety
of steps, but isn't as flexible and capable as an advanced
assembler. In short, it is hardly the last word in
nanotechnology, yet is a great advance over what has gone
before.

Products

With its ability to accelerate desired
reactions by a factor of a million or so, the U. Brob team's
molecular manipulator can perform 10,000 to 100,000 steps
with good reliability. Back in the 1980s, chemists making
protein molecules struggled to perform just one hundred
steps. The U. Brob research team (and its many imitators) can
now build structures that are stronger and easier to design
than proteins: not floppy, folded chains, but rugged objects
held together by a sturdy network of bonds. Though not as
strong and dense as diamond, these structures are like bits
of a tough engineering plastic. A specially adapted
computer-aided design system makes it easy to design
molecular objects made from these materials.

Yet the AFM-based molecular manipulator has
one grave disadvantage: It does chemistry one molecule at a
time, and it ties up a machine as expensive as a car for
hours or days to produce that one large molecule. Some
molecules, though, are valuable enough to be worth building
even one at a time. These draw prompt attention.

A single molecule isn't much use as a dye, a
drug, or a floor wax, but it can have substantial value if it
provides useful information. The U. Brob team quickly
publishes a pile of scientific papers based on experiments
with single molecules: they build a molecule, probe it,
report the results, and build another. Some of these results
show chemists elsewhere in the multibillion-dollar chemical
industry how to design new catalysts, molecules that can help
make other molecules more cheaply, cleanly, and efficiently.
This information is worth a lot.

Three new products of special interest are
among the first to be made. The firstmolecular
electronicsbegins with experiments conducted by a
research group at a computer chip company. They use their
molecular manipulator to build single molecules and probe
them, gradually learning how to build the parts needed for
molecular electronic computers. These new computers don't
immediately become practical, because the costs are too high
for making such large molecules with AFM-based technology.
Yet some companies begin to produce simpler molecular
electronic devices for use in sensors and specialized
high-speed signal processing. A specialty industry is born
and begins to expand.

The second product is a gene reader, a
complex molecular device built on the surface of a chip. The
biologists who built the reader combined proteins borrowed
from cells with
special-purpose molecular
machines designed from scratch. The result was a
molecular system that binds DNA
molecules and pulls them past a read-head-like tape through a
tape recorder. The device works as fast as some naturally
occurring molecular machines that read DNA, with one key
advantage: it outputs its data electronically. At that speed,
a single device can read a human genome in about a year.
Though still too expensive for a doctor's office, these
readers are promptly in great demand from research
laboratories. Another small industry is born.

The third product is far more important, in
the long run: replacement tips for molecular manipulators,
grippers, and tools that are better than the originals. With
these new, more versatile devices, researchers are now
building more ambitious products and tools.

More Scenario: The Next
Step to Nanotechnology

While the physicist-led team at U. Brob was
finishing its work on the AFM-based molecular manipulator, a
chemist-led team at the University of Lilliput was working
furiously. They saw the U. Brob desktop machine as too large
and its expected products as too expensive. Even back in the
1980s, David Biegelsen of the Xerox Palo Alto Research Center
had noted, "The main drawback I see to using a hybrid
protoassembler [AFM-based molecular manipulator] is that it
would take a long time to build just one unit. Building
requires a series of atom-by-atom construction steps. It
would be better to build in parallel from the very beginning,
making many trillions of these molecules all at the same
time. I think there is tremendous power in parallel assembly.
Maybe another field, chemistry or biology, offers a better
way to do it." The chemists at U. Lill aimed to develop
that better way, building first simple and then more and more
complex molecular machines. The eventual result was a
primitive molecular assembler able to build molecular objects
by the trillions.

Chemist's Tools

How did the chemists achieve this? During the
years when the U. Brob team was developing the molecular
manipulator, researchers working in protein science and synthetic
chemistry had made better and better systems of molecular
building blocks. Chemists were well prepared for doing this: by
the late 1980s, it had become possible to build stable structures
the size of medium-sized protein molecules, and work had begun to
focus on making these molecules perform useful work by binding
and modifying other molecules. Chemists learned to use these
sophisticated catalysts-early molecular devices-to make their own
work easier by helping in the manufacture of still more large
molecules.

Another traditional chemist's tool was software
for doing computer-aided design. The early software designed by Jay Ponder and Frederic
Richards of Yale University ultimately led to semi-automatic
tools for designing molecules of a particular shape and function.
Chemists then could easily design molecules that would
self-assemble into larger structures, several tens of nanometers
across.

Molecular Construction
Machines

These advances in software and chemical
synthesis let the U. Lill team tackle the task of building a
primitive version of a molecular assembler. Although they
couldn't build anything as complex as a nanocomputer or as
stiff as diamond, they didn't need to. Their design used
sliding molecular rods to position a molecular gripper much
like the gripper used at U. Brob, again using the surrounding
liquid to control which tool the gripper held. Instead of an
AFM's electronic controls, they used the surrounding liquid
to control the position of the rods as well. In a neutral
solution, the rods would withdraw; in an acid solution, they
would extend. How far they moved depended on what other
molecules were around to lodge in special pockets and block
the motion.

Their primitive assemblers built much the
same sorts of products that the U. Brob molecular manipulator
did; the tools were similar, and speed and accuracy were
about the same. Yet there was one dramatic advantage: About
1,000,000,000,000,000,000,000 U. Lill assemblers could fit in
the space occupied by one U. Brob manipulator, and it was
easy to produce a mere 1,000,000,000,000,000 times as much
product at the same cost.

With the first, primitive assemblers,
construction was slow because each step required new liquid
baths and several seconds of soaking and waiting, and a
typical product might take thousands of steps. Nonetheless,
the U. Lill team made a lot of money licensing their
technology to researchers trying to commercialize products
they had first researched with the U. Brob machine. After
starting an independent company (Nanofabricators, Inc.), they
poured their research efforts into building better machines.
Within a few years, they had assemblers with multiple
grippers, each loaded with a different kind of tool; flashes
of colored light would flip molecules from state to state
(they copied these molecules from the pigments of the retina
of the eye); flipping molecules would change tools and change
rod positions. Soaking and waiting become a thing of the
past, and soon they were pouring out parts that, when mixed
with liquid and added to dishes with special blank chips
would build up the dense memory layers that made possible the
Pocket Library.

That was when things started moving fast. The
semiconductor industry went the way of the vacuum tube
industry. Money and talent poured into the new technology.
Molecular CAD tools got better, assemblers made it easy to
build what was designed, and fast production and testing made
molecular engineering as easy as playing with software.
Assemblers got better, faster, and cheaper. Researchers used
assemblers to build nanocomputers, and nanocomputers to
control better, faster assemblers. Using tools to build
better tools is an ancient story. Within a decade, almost
anything could be made by molecular manufacturing, and was.

FIGURE 7: PATHS TO NANOTECHNOLOGY

Nanotechnology development flow chart

Will developments in the late pre-breakthrough
days be as just described? Certainly not: the technical
approaches will differ, and the U.S. academic research setting
implied by the scenario could easily be replaced by academic,
commercial, governmental, or military research settings in any of
the advanced nations. What do seem realistic are the implied
requirements for effort, technology, and time, as well as the
basic capabilities of different devices. We are approaching a
threshold of capability beyond which further advances will become
easy and fast.